High-throughput screening of a 100,000-compound library for inhibitors of influenza A virus (H3N2)

J Biomol Screen. 2008 Oct;13(9):879-87. doi: 10.1177/1087057108323123. Epub 2008 Sep 23.


Using a highly reproducible and robust cell-based high-throughput screening (HTS) assay, the authors screened a 100,000-compound library at 14- and 114-microM compound concentration against influenza strain A/Udorn/72 (H3N2). The "hit" rates (>50% inhibition of the viral cytopathic effect) from the 14- and 114-microM screens were 0.022% and 0.38%, respectively. The hits were evaluated for their antiviral activity, cell toxicity, and selectivity in dose-response experiments. The screen at the lower concentration yielded 3 compounds, which displayed moderate activity (SI(50) = 10-49). Intriguingly, the screen at the higher concentration revealed several additional hits. Two of these hits were highly active with an SI(50) > 50. Time of addition experiments revealed 1 compound that inhibited early and 4 other compounds that inhibited late in the virus life cycle, suggesting they affect entry and replication, respectively. The active compounds represent several different classes of molecules such as carboxanilides, 1-benzoyl-3-arylthioureas, sulfonamides, and benzothiazinones, which have not been previously identified as having antiviral/anti-influenza activity.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antiviral Agents / pharmacology*
  • Automation
  • Cell Line
  • Chemistry, Pharmaceutical / methods
  • Dogs
  • Drug Design
  • Drug Evaluation, Preclinical / methods*
  • Influenza A Virus, H3N2 Subtype / chemistry*
  • Inhibitory Concentration 50
  • Models, Chemical
  • Ribavirin / pharmacology
  • Virus Replication / drug effects


  • Antiviral Agents
  • Ribavirin